title: Modeling interleukin-2-based immunotherapy in AIDS pathogenesis.
abstract: In this paper, we sought to identify the CD4(+) T-cell dynamics in the course of HIV infection in response to continuous and intermittent intravenous courses of interleukin-2 (IL-2), the principal cytokine responsible for progression of CD4(+) T-lymphocytes from the G1 to the S phase of the cell cycle. Based on multivariate regression models, previous literature has concluded that the increase in survival of CD4(+) T-cell appears to be the critical mechanism leading to sustained CD4(+) T-cell levels in HIV-infected patients receiving intermittent IL-2 therapy. Underscored by comprehensive mathematical modeling, a major finding of the present work is related to the fact that, rather than due to any increase in survival of CD4(+) T-cells, the expressive, selective and sustained CD4(+) T-cell expansions following IL-2 administration may be related to the role of IL-2 in modulating the dynamics of Fas-dependent apoptotic pathways, such as activation-induced cell death (AICD) or HIV-specific apoptotic routes triggered by viral proteins.
authors.affiliation: Process Control and Simulation Laboratory, University of São Paulo, Av. Prof. Luciano Gualberto, Trav. 3, São Paulo SP 05508-900, Brazil. joly@petrobras.com.br
authors.forename: Marcel
authors.initials: M
authors.lastname: Joly
authors.forename: Darci
authors.initials: D
authors.lastname: Odloak
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D005260:Female; D016193:G1 Phase / Q000187:drug effects / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000276:immunology / Q000627:therapeutic use; D008297:Male; D016196:S Phase / Q000187:drug effects / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology; D019014:fas Receptor / Q000276:immunology
chemical_list: C491901:FAS protein, human; C508594:IL2 protein, human; D007376:Interleukin-2; D014764:Viral Proteins; D019014:fas Receptor
keywords: AICD; AIDS; APC; CCF; CNS; DAE; ENV; Env-CD4 cross-linking mediated apoptosis; FDC; HAART; HEV; HIV; IFN-γ; IL-12; IL-2; IU; IVST; Immune system; Immunotherapy; International Unit; LT; MHC; MIU; PB; PCD; PCR; PSVE; T-lymphocyte; TAT; Tat-induced apoptosis; VTC; acquired immunodeficiency syndrome; activation-induced cell death; antigen presenting cells; cell–cell fusion; central nervous system compartment; differential-algebraic equations; follicular dendritic cells; high endothelial venules; highly active antiretroviral therapy; human immunodeficiency virus; interferon γ; interleukin-12; interleukin-2; intracellular viral stock transference; lymphoid tissue compartment; major histocompatibility complex; million International Units; passive cell death; peripheral blood compartment; polarized secretion of viral envelopes; polymerase chain reaction; virus-to-cell